Abstract
OBJECTIVES: Response surface methodology coupled with statistically designed experiments has been found to be very useful in optimising multivariable processes. The aim of this study was to evaluate the influence of two independent variables, a ratio of permeation enhancers/antioxidants (transcutol and ethanolic extract of tetracarpidium conophorum EETC) and stirring rate, on the flux and permeation of gentamicin hydrogel. MATERIALS AND METHODS: A modification of free radical initial polymerization was used to formulate the gentamicin hydrogel. A 32 factorial CCD was then used to investigate the effect of independent variables of the permeation enhancer transcutol: EETC (X1), stirring speed (X2) via 14 formulation batches, which were evaluated for dependent variables flux (Y1) and amount of drug permeated after 12 hours (Y2) ex vivo. RESULTS: The results of ANOVA performed to determine the fit of the models revealed that the models were statistically significant (p<0.05) and did not show lack of fit (R2>0.80). The regression equation generated for flux was Y1=19.35 - 25.82X1 - 0.044X2 + 0.0097X1X2 + 11.86X21 and for cumulative permeation of gentamicin in 12 hours Y2=315.50 - 189.67X1 + 0.28X2 -1.29X1X2 + 123.55X21. The validity of the statistical models used for predicting flux and drug permeation was confirmed by conducting three confirmation experimental runs at the identified optimum conditions. The results showed that there was no significant difference between the experimental results and those predicted by the statistical models. CONCLUSION: The excellent correlation between the predicted and measured values shows the validity of statistical models (R2=0.95). An antioxidant and permeation enhancer has been used for the first time to investigate the influence on dependent variables. Optimization of gentamicin hydrogel using central composite statistical design is valid for the prediction of drug permeation and flux using variables in formulation.